Linezolid is a synthetic antibacterial agent. Chemically, it is (S)—N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide. The empirical formula is C16H20FN3O4. Its molecular weight is 337.35.
Linezolid is used in the treatment of vancomycin-resistant enterococcus faecium infections; nosocomial pneumonia; complicated skin and skin structure infections including diabetic foot infections, without concomitant osteomyelitis; uncomplicated skin and skin structure infections and community acquired pneumonia.
Linezolid is sold in the U.S. under the brand name(s) of ZYVOX® I.V. Injection, ZYVOX Tablets, and ZYVOX for Oral Suspension. Tablets were given two to three times a day.
Linezolid and its salts are described in U.S. Pat. No. 5,688,792. Crystalline form I and II are known polymorphs of Linezolid. Crystalline form I of linezolid was described by J. Med. Chem. 39(3), 673-679, 1996.
U.S. Pat. No. 6,559,305 discloses a crystalline linezolid form II.
WO2007/102082 assigned to Glenmark Pharmaceuticals Ltd discloses compositions of Linezolid crystalline Form II containing lactose-based water soluble excipient.
In the recent years, a new polymorph of linezolid, namely form III, was discovered and described in U.S. Pat. No. 7,714,128. The crystalline form III was characterized by an x-ray powder diffraction spectrum having peaks expressed as 2θ at about 7.6, 9.6, 13.6, 14.9, 18.2, 18.9, 21.2, 22.3, 25.6, 26.9, 27.9 and 29.9 degrees.
U.S. Publication no. 2007/0104785 discloses a manufacture of the solid oral dosage form of linezolid Form III. It describes a gelling potential of linezolid Form III which affects the reproducibility of dissolution. The manufacturing of the dosage form with reproducible dissolution profile was achieved by using effervescent couple (or) by incorporating water insoluble polymers (or) by adding clays in the dosage form (or) combinations thereof.
WO 2010/026597 assigned to Hetero discloses a multiparticulate composition which requires forming a core in the form of beadlet or pellet manufactured by extrusion and spheronization method, where the core comprises linezolid form III, one or more binders, and one or more disintegrants. Both processes require either special material or equipment which are not desirable for commercial production.
There is a need to develop a composition and its process for manufacturing a solid unit dosage form comprising linezolid form III which retains its polymorphic form and stable during manufacturing process and throughout the shelf life.